Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing

Abstract BACKGROUND Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy. METHODS NIPT cases that showed a distortion from normal euploid genomic representation were communicated to the caregiving physician as nonreportable for fetal aneuploidy. Follow-up information was subsequently collected for these cases. More than 450000 pregnant patients who submitted samples for clinical laboratory testing >3 years are summarized. Additionally, in-depth analysis was performed for >79000 research-consented samples. RESULTS In total, 55 nonreportable NIPT cases with altered genomic profiles were cataloged. Of these, 43 had additional information available to enable follow-up. A maternal neoplasm was confirmed in 40 of these cases: 18 malignant, 20 benign uterine fibroids, and 2 with radiological confirmation but without pathological classification. CONCLUSIONS In a population of pregnant women who submitted a blood sample for cfDNA testing, an abnormal genomic profile not consistent with fetal abnormalities was detected in about 10 out of 100000 cases. A subset of these observations (18 of 43; 41.9%) was attributed to maternal malignant neoplasms. These observational results suggest the need for a controlled trial to evaluate the potential of using cfDNA as an early biomarker of cancer.

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Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples

Prenatal Diagnosis ◽

10.1002/pd.4123 ◽

2013 ◽

Vol 33 (6) ◽

pp. 569-574 ◽

Cited By ~ 129

Author(s):

Tracy Futch ◽

John Spinosa ◽

Sucheta Bhatt ◽

Eileen Feo ◽

Richard P. Rava ◽

...

Keyword(s):

Clinical Laboratory ◽

Prenatal Testing ◽

Maternal Plasma ◽

Plasma Dna ◽

Noninvasive Prenatal Testing ◽

Laboratory Experience ◽

Fetal Aneuploidy

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Simultaneous detection of fetal aneuploidy, de novo FGFR3 mutations and paternally derived β‐thalassemia by a novel method of noninvasive prenatal testing

Prenatal Diagnosis ◽

10.1002/pd.5879 ◽

2020 ◽

Author(s):

Lin Yang ◽

Yujing Wu ◽

Zhiyang Hu ◽

Haiping Zhang ◽

Dandan Pu ◽

...

Keyword(s):

De Novo ◽

Simultaneous Detection ◽

Prenatal Testing ◽

Noninvasive Prenatal Testing ◽

Fetal Aneuploidy ◽

Novel Method ◽

Fgfr3 Mutations

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Noninvasive Prenatal Testing for Fetal Aneuploidy

Obstetrics and Gynecology ◽

10.1097/aog.0b013e31828642c6 ◽

2013 ◽

Vol 121 (4) ◽

pp. 847-850 ◽

Cited By ~ 49

Author(s):

Mary E. Norton ◽

Nancy C. Rose ◽

Peter Benn

Keyword(s):

Prenatal Testing ◽

Noninvasive Prenatal Testing ◽

Fetal Aneuploidy

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Parental willing to take invasive diagnosis after Expanded Noninvasive Prenatal Testing (expanded NIPT) in a cohort of 24768 cases

10.21203/rs.3.rs-21668/v1 ◽

2020 ◽

Author(s):

Yunsheng Ge ◽

Jia Li ◽

Jianlong Zhuang ◽

Jian Zhang ◽

Yanru Huang ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Prenatal Testing ◽

High Sensitivity ◽

Copy Number Variations ◽

Noninvasive Prenatal Testing ◽

Predictive Values ◽

Prenatal Test ◽

Xyy Syndrome ◽

Chromosomal Aneuploidies

Abstract BackgroundThe main aims of the study were to investigate the performance of expanded noninvasive prenatal test (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs) and copy number variations (CNVs) and parental willing to taking invasive prenatal diagnosis after expanded NIPT in China.ResultsOf the 24,736 cases, successful follow-up was conducted in 92.2% (411/446) cases. The sensitivity of expanded NIPT test was 98.61%,90.91% and 100% and specificity was 99.91%,99.95% and 99.87% for the detection of trisomies 21, 18 and 13 respectively. Expanded NIPT detected 45, XO, 47, XXX, 47, XXY, XYY syndrome, RATs and CNVs with positive predictive values of 57.39%, 19.61%, 75%, 79.41%, 77.78%, 10% and 56.25% respectively. The women carrying fetuses with T21/T18/T13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those positive for SCAs, RATs and CNVs.ConclusionsOur study demonstrates that the expanded NIPT detects fetal trisomies 21,18 and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs and CNVs is still relatively poor and needed to be improved. With a positive expanded NIPT result, the women at high risk for common trisomies are more willing to take invasive prenatal diagnosis and terminate their pregnancies.* the first two authors contribute equally to this study.

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Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome

Fetal Diagnosis and Therapy ◽

10.1159/000519057 ◽

2021 ◽

pp. 1-6

Author(s):

Tzu-Yi Lin ◽

T’sang-T’ang Hsieh ◽

Po-Jen Cheng ◽

Tai-Ho Hung ◽

Kok-Seong Chan ◽

...

Keyword(s):

High Risk ◽

Digeorge Syndrome ◽

Prenatal Testing ◽

Cardiac Anomaly ◽

Comparative Genomic ◽

Noninvasive Prenatal Testing ◽

Maternal Fetal Medicine ◽

Chromosome 22Q11 ◽

Predictive Rate

Objective: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. Methods: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. Results: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57–100.00%) and 99.92% (95% CI 99.83–99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14–76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. Discussion/Conclusion: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

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Noninvasive prenatal testing for fetal aneuploidy and single gene disorders

Best Practice & Research Clinical Obstetrics & Gynaecology ◽

10.1016/j.bpobgyn.2017.02.007 ◽

2017 ◽

Vol 42 ◽

pp. 26-38 ◽

Cited By ~ 27

Author(s):

Hannah Skrzypek ◽

Lisa Hui

Keyword(s):

Single Gene ◽

Prenatal Testing ◽

Noninvasive Prenatal Testing ◽

Fetal Aneuploidy ◽

Single Gene Disorders

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Noninvasive Prenatal Testing for Fetal Aneuploidy in Argentina

AJOB Empirical Bioethics ◽

10.1080/23294515.2014.993439 ◽

2015 ◽

Vol 6 (1) ◽

pp. 111-114 ◽

Cited By ~ 4

Author(s):

Lucas Otaño ◽

Laura Igarzábal

Keyword(s):

Prenatal Testing ◽

Noninvasive Prenatal Testing ◽

Fetal Aneuploidy

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Uterine artery embolization or myomectomy for women with uterine fibroids: four-year follow-up of a randomised controlled trial

European Journal of Obstetrics & Gynecology and Reproductive Biology X ◽

10.1016/j.eurox.2021.100139 ◽

2021 ◽

pp. 100139

Author(s):

Jane Daniels ◽

Lee J. Middleton ◽

Versha Cheed ◽

William McKinnon ◽

Fusun Sirkeci ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Uterine Artery Embolization ◽

Uterine Artery ◽

Controlled Trial ◽

Uterine Fibroids ◽

Artery Embolization ◽

Randomised Controlled

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Audit of the first > 7500 noninvasive prenatal aneuploidy tests in a Swiss genetics center

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-021-06203-7 ◽

2021 ◽

Author(s):

Anahita Bajka ◽

Michael Bajka ◽

Fabian Chablais ◽

Tilo Burkhardt

Keyword(s):

Pregnancy Outcome ◽

False Positive Rate ◽

Prenatal Testing ◽

Accurate Method ◽

Test Results ◽

Data Set ◽

Single Nucleotide ◽

Noninvasive Prenatal Testing ◽

Positive Rate

Abstract Objectives Noninvasive prenatal testing (NIPT) is actually the most accurate method of screening for fetal chromosomal aberration (FCA). We used pregnancy outcome record to evaluate a complete data set of single nucleotide polymorphism-based test results performed by a Swiss genetics center. Materials and methods The Panorama® test assesses the risk of fetal trisomies (21, 18 and 13), gonosomal aneuploidy (GAN), triploidy or vanishing twins (VTT) and five different microdeletions (MD). We evaluated all 7549 test results meeting legal and quality requirements taken in women with nondonor singleton pregnancies between April 2013 and September 2016 classifying them as high or low risk. Follow-up ended after 9 months, data collection 7 months later. Results The Panorama® test provided conclusive results in 96.1% of cases, detecting 153 FCA: T21 n = 76, T18 n = 19, T13 n = 15, GAN n = 19, VTT n = 13 and MD n = 11 (overall prevalence 2.0%). Pregnancy outcome record was available for 68.6% of conclusive laboratory results, including 2.0% high-risk cases. In this cohort the Panorama® test exhibited 99.90% sensitivity for each trisomy; specificity was 99.90% for T21, 99.98% for T18 and 99.94% for T13. False positive rate was 0.10% for T21, 0.02% for T18 and 0.06% for T13. Conclusion SNP-based testing by a Swiss genetics center confirms the expected accuracy of NIPT in FCA detection.

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